Dynamic modulation of postnatal development of preconfigured and plastic time-compressed sequences

预配置和可塑时间压缩序列的出生后发育的动态调节

• 批准号: 10227790
• 负责人: GEORGE DRAGOI
• 金额: $ 41.88万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-24 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10227790
• 关键词: Address; Adult; Affect; Age; Amnesia; Animals; Area; Behavioral; Binding; Birth; Brain; Brain Diseases; Cells; Characteristics; Chronic; Code; Complex; Computing Methodologies; Dependence; Development; Electrophysiology (science); Enhancers; Episodic memory; Event; Eye; Goals; Hippocampus (Brain); Home; Human; Infusion procedures; Intellectual functioning disability; Lead; Life; Life Experience; Location; Memory; Nerve Growth Factors; Neurons; Operating System; Pattern; Process; Psyche structure; Rattus; Reporting; Rest; Rodent; Role; Schizophrenia; Sleep; Suggestion; Synaptic plasticity; Therapeutic Intervention; Time; Visual; age related; autism spectrum disorder; awake; cognitive function; critical developmental period; dark rearing; early onset; environmental enrichment for laboratory animals; experience; infancy; memory consolidation; memory encoding; neuropsychiatric disorder; neuropsychiatry; novel; postnatal; postnatal development; preservation; preventive intervention; programs; relating to nervous system; visual deprivation

Project summary: Of the multiple memory systems operating in the brain, episodic memory, defined by the ability to remember where and when events occurred in the past, is a recently evolved, later developing and early deteriorating cognitive function. Early-life episodic memories are rapidly forgotten, a phenomenon known as infantile amnesia occurring in humans and non-human animals. The hippocampus, an evolutionarily ancient, highly organized part of the cortex, is essential for the relational binding of spatial locations and events into spatial and mental trajectories and memory episodes. The rapid encoding and consolidation of sequential spatial experiences into memory episodes is believed to be achieved by the representation of such trajectories within time-compressed hippocampal ‘place cell’ sequences during navigation and the sleep/rest periods preceding (i.e., preplay, supporting rapid encoding) and following (i.e., replay, supporting consolidation) the novel experiences. The hippocampus undergoes a developmental critical period and functionally matures around postnatal day 24 (P24) in the rat, an age when infantile amnesia ends in rodents. Our main goal is to explore and understand the dependence of memory development on intrahippocampal synaptic plasticity and early-life experience by studying the development of ensemble place cell coding in the hippocampus. We combine chronic electrophysiologic recording of large ensembles of neurons in awake-behaving and sleeping rats across three recently described developmental stages in postnatal life with intra-hippocampal infusion of enhancers of synaptic plasticity, rearing in enriched environments or early-life visual deprivation (dark rearing), and computational methods for decoding spatial trajectories. The successful completion of our proposed aims promises to uncover such developmental mechanism and factors in the rat, which should help understand the development and emergence of episodic memories in the human, where such invasive approaches are not possible. Our findings could more generally impact our understanding of developmental neuro-psychiatric brain diseases like autism, schizophrenia, and intellectual disabilities.

项目概述：在大脑中运行的多个记忆系统中，情景记忆，由 记忆过去事件发生的地点和时间的能力，是最近发展起来的，后来发展起来的， 早期认知功能恶化早期生活中的情景记忆会很快被遗忘，这是一种众所周知的现象。 婴儿期失忆症发生在人类和非人类动物身上海马体，一个进化上 大脑皮层的一个古老的、高度组织化的部分，对于空间位置和事件的关系绑定至关重要 空间和精神轨迹以及记忆片段。序列的快速编码与合并 空间经验转化为记忆片段被认为是通过这种轨迹的表征来实现的 在导航和睡眠/休息期间， 在前（即，预播放，支持快速编码）和后续（即，重播，支持合并）， 新奇的体验。海马经历一个发育的关键期，功能成熟 大鼠出生后第24天（P24）左右，这是啮齿类动物婴儿期健忘症结束的年龄。我们的主要目标是 探索和理解记忆发展对海马内突触可塑性的依赖性， 通过研究海马体中整体位置细胞编码的发展来了解早期生活经验。我们 联合收割机对清醒和睡眠时大量神经元的慢性电生理记录 大鼠在出生后的三个最近描述的发育阶段，海马内注入 突触可塑性的增强剂，在丰富的环境中饲养或早期视觉剥夺（黑暗饲养）， 以及用于解码空间轨迹的计算方法。成功实现我们的既定目标 有望揭示大鼠的这种发育机制和因素，这将有助于了解 人类情景记忆的发展和出现，在这种侵入性方法不 可能我们的发现可能会更普遍地影响我们对发育神经精神脑的理解 自闭症、精神分裂症和智力障碍等疾病。